Trends in prescriptions for sedative–hypnotics among Korean adults: a nationwide prescription database study for 2011–2015

Lee, Mi Hyun; Choi, Jae Won; Lee, Joonki; Shin, Aesun; Oh, Seong Min; Jung, Sun Jae; Lee, Yu Jin

doi:10.1007/s00127-018-1615-x

Cited by 31 publications

(31 citation statements)

References 25 publications

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“…Our findings are consistent with those from a cross-sectional study in Japanese adults with insomnia from the 2012 Japan National Health and Wellness Survey [ 14 ], which reported BZDs and non-BZDs (zolpidem, brotizolam, flunitrazepam, etizolam and triazolam) as the most commonly prescribed hypnotic drugs. Similar trends were reported in studies in the USA, Taiwan, South Korea, France and Switzerland [ 15 – 19 ]. Thus, the high prevalence of BZD receptor agonist prescription remains a challenge in public health systems worldwide.…”

Section: Discussionsupporting

confidence: 89%

Prescribing Pattern of Hypnotic Medications in Patients Initiating Treatment at Japanese Hospitals: A Nationwide, Retrospective, Longitudinal, Observational Study Using a Claims Database

Inada

Enomoto

Yamato

et al. 2021

Drugs - Real World Outcomes

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Background Prolonged treatment of insomnia using benzodiazepine (BZD) receptor agonists, including BZD and non-BZD hypnotic drugs, can cause drug dependence, tolerance, abuse and other adverse events. These side effects are more common and/or severe in older adults taking different hypnotic drugs concomitantly. Therefore, a single prescription is limited to 30 daily doses for most BZD receptor agonists and restrictions apply to the prescription of more than three types of hypnotic drugs in Japan. Little is known, however, about the real-world prescribing pattern of hypnotic drugs in Japan. Objective We analysed prescribing patterns for hypnotic drugs in Japan to evaluate whether real-world use differs from guideline recommendations. Methods In this nationwide, retrospective, longitudinal, observational study, we analysed the types of hypnotic drugs prescribed, duration of medication and treatment setting in a subset of hospitals in Japan using a hospital-based administrative claims database (Medical Data Vision). Patients initiating treatment with hypnotic drugs between January 2012 and December 2016 were included in the analyses to assess the duration of medication and occurrence of co-prescription of a second and third hypnotic drug, within a year from prescription of the first hypnotic drugs. Results In 261,167 patients analysed, the first hypnotic drugs prescribed were BZDs (59.7%), non-BZDs (36.8%), a melatonin receptor agonist [MRA] (3.1%) and an orexin receptor antagonist [ORA] (0.4%). Benzodiazepine and non-BZD hypnotic drugs were mostly prescribed in inpatient settings (57.7% and 63.0%, respectively) and the MRA and ORA mostly in outpatient settings (62.6% and 65.4%, respectively). The departments that prescribed the most patients their first hypnotic drugs were internal medicine (23.6%), general surgery (11.8%), orthopaedic surgery (11.4%) and urology (5.3%). Of the total prescriptions of MRA and ORA as the first hypnotic drugs, 22.0% and 31.8% were in internal medicine, 4.4% each in general surgery, 6.0% and 4.5% in orthopaedic surgery, 9.7% and 4.4% in neurology, and 10.1% and 12.2% in psychiatry departments, respectively. Mean duration of medication was 1.13 months for non-BZDs, 1.15 months for BZDs, 1.29 months for the ORA and 1.83 months for the MRA. Overall, 5.3% (95% confidence interval 5.2–5.4) of patients were prescribed a second hypnotic drug; of these, 8.4% (95% confidence interval 8.0–8.9) were prescribed at least three hypnotic drugs within a year. Patients who were prescribed three or more hypnotic drugs received higher doses of the first drug than patients who received fewer hypnotic drugs. Conclusions Benzodiazepine receptor agonists were the most common hypnotic drugs prescribed as the first drug to patients in Japan. Further education and awareness may be needed on the risk of complications and adverse events associated with these therapies. The duration ...

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Section: Discussionsupporting

confidence: 89%

Prescribing Pattern of Hypnotic Medications in Patients Initiating Treatment at Japanese Hospitals: A Nationwide, Retrospective, Longitudinal, Observational Study Using a Claims Database

Inada

Enomoto

Yamato

et al. 2021

Drugs - Real World Outcomes

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“…Zolpidem is also a recommended treatment for patients with insomnia in Korea, where it is currently the most widely used hypnotic agent. Similar to other countries, it has been found that sedative-hypnotics are more frequently prescribed to female patients than males 3 .…”

Section: Introductionsupporting

confidence: 56%

Effect of CYP3A4 metabolism on sex differences in the pharmacokinetics and pharmacodynamics of zolpidem

Yoon

Jeong

Jung

et al. 2021

Sci Rep

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To investigate pharmacokinetic and pharmacodynamic differences of zolpidem between males and females and their causes, including CYP3A4 activity. A single oral dose of zolpidem (10 mg) was administered to 15 male and 15 female healthy subjects. Blood samples were collected up to 12 h post-dose to determine plasma zolpidem concentrations. Pharmacokinetic parameters were obtained using non-compartmental analysis. Digit symbol substitution test, choice reaction time, and visual analog scale of sleepiness were used to evaluate pharmacodynamics. We measured CYP3A4 activity using 4β-hydroxycholesterol, an endogenous metabolite. Mean maximum plasma concentration and area under the plasma concentration–time curve were higher for females than for males (9.9% and 32.5%, respectively); other pharmacokinetic parameters showed no significant differences. Pharmacodynamic scores for females showed delayed recovery compared with that for males. CYP3A4 activity was higher in females than in males (p = 0.030). There was no serious adverse event, and adverse event incidence was not different between the sexes. Zolpidem exposure was about 30% higher in females than in males. Delayed pharmacodynamic score recovery in females could be related to higher zolpidem concentrations. Although apparent clearance was lower in females, systemic clearance might not be the cause of the different exposures to zolpidem.

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“…Zolpidem, in particular, was prescribed 1.6 times more frequently for women compared to men. 45 This is particularly relevant, as recent research revealed important sex-specific differences in the pharmacokinetic profile of this class of drugs. In fact, because slower drug metabolism among women could lead to outsized psychoactive effects compared to men at the same dose, the FDA has reduced the recommended dose of zolpidem by 50%.…”

Section: Sex and Insomnia Treatmentmentioning

confidence: 99%

Elucidating the Relationship Between Insomnia, Sex, and Cardiovascular Disease

Leeds

Shechter

Alcántara

et al. 2020

Gender and the Genome

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Sex differences in cardiovascular disease (CVD) mortality have been attributed to differences in pathophysiology between men and women and to disparities in CVD management that disproportionately affect women compared to men. Similarly, there has been investigation of differences in the prevalence and presentation of insomnia attributable to sex. Few studies have examined how sex and insomnia interact to influence CVD outcomes, however. In this review, we summarize the literature on sex-specific differences in the prevalence and presentation of insomnia as well as existing research regarding the relationship between insomnia and CVD outcomes as it pertains to sex. Research to date indicate that women are more likely to have insomnia than men, and there appear to be differential associations in the relation between insomnia and CVD by sex. We posit potential mechanisms of the relationship between sex, insomnia and CVD, discuss gaps in the existing literature, and provide commentary on future research needed in this area. Unraveling the complex relations between sex, insomnia, and CVD may help to explain sex-specific differences in CVD, and identify sex-specific strategies for promotion of cardiovascular health. Throughout this review, terms “men” and “women” are used as they are in the source literature, which does not differentiate between sex and gender. The implications of this are also discussed.

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Trends in prescriptions for sedative–hypnotics among Korean adults: a nationwide prescription database study for 2011–2015

Cited by 31 publications

References 25 publications

Prescribing Pattern of Hypnotic Medications in Patients Initiating Treatment at Japanese Hospitals: A Nationwide, Retrospective, Longitudinal, Observational Study Using a Claims Database

Prescribing Pattern of Hypnotic Medications in Patients Initiating Treatment at Japanese Hospitals: A Nationwide, Retrospective, Longitudinal, Observational Study Using a Claims Database

Effect of CYP3A4 metabolism on sex differences in the pharmacokinetics and pharmacodynamics of zolpidem

Elucidating the Relationship Between Insomnia, Sex, and Cardiovascular Disease

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